Serum Lycopene, Lutein and Zeaxanthin, and the Risk of Alzheimer's Disease Mortality in Older Adults

Background: Oxidative stress is implicated in the pathogenesis of Alzheimer's disease (AD). Accumulating evidence shows that antioxidant-rich food reduces the risk of AD by inhibiting oxidative stress. This study investigates whether serum levels of carotenoids were associated with the risk of AD mortality in a nationally representative sample of US adults. Methods: We used data from the Third Nutrition and Health Examination Survey (NHANES III) database and the NHANES III Linked Mortality File. A total of 6,958 participants aged older than 50 years were included in this study. Results: We found that high serum levels of lycopene and lutein+zeaxanthin at baseline were associated with a lower risk of AD mortality after adjustment for potential covariates. The reduction in the mortality risk was progressively raised by increasing serum lycopene (HR = 0.26, 95% CI 0.10-0.69) and lutein+zeaxanthin (HR = 0.43, 95% CI 0.22-0.85) levels. In contrast, no associations with AD mortality were observed for other serum carotenoids, including alpha-carotene, beta-carotene, and beta-cryptoxanthin. Conclusion: High serum levels of lycopene and lutein+zeaxanthin are associated with a lower risk of AD mortality in adults. Our findings suggest that a high intake of lycopene- or lutein+zeaxanthin-rich food may be important for reducing the AD mortality risk.

[1]  H M Rosenberg,et al.  Comparability of cause of death between ICD-9 and ICD-10: preliminary estimates. , 2001, National vital statistics reports : from the Centers for Disease Control and Prevention, National Center for Health Statistics, National Vital Statistics System.

[2]  M. Murakoshi,et al.  Carotenoids in Cancer Chemoprevention , 2004, Cancer and Metastasis Reviews.

[3]  R Clarke,et al.  Folate, vitamin B12, and serum total homocysteine levels in confirmed Alzheimer disease. , 1998, Archives of neurology.

[4]  J. Potter,et al.  Plasma carotenoids as biomarkers of vegetable and fruit intake. , 1994, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[5]  J. Quinn,et al.  Nutritional biomarkers in Alzheimer's disease: the association between carotenoids, n-3 fatty acids, and dementia severity. , 2008, Journal of Alzheimer's disease : JAD.

[6]  I. Young,et al.  Plasma chain-breaking antioxidants in Alzheimer's disease, vascular dementia and Parkinson's disease. , 1999, QJM : monthly journal of the Association of Physicians.

[7]  P. Di Mascio,et al.  Lycopene as the most efficient biological carotenoid singlet oxygen quencher. , 1989, Archives of biochemistry and biophysics.

[8]  W. Stahl,et al.  Lycopene: a biologically important carotenoid for humans? , 1996, Archives of biochemistry and biophysics.

[9]  C. Berr,et al.  Plasma carotenoid levels and cognitive performance in an elderly population: results of the EVA Study. , 2007, The journals of gerontology. Series A, Biological sciences and medical sciences.

[10]  D. Albanes,et al.  Intake of Flavonoids, Carotenoids, Vitamins C and E, and Risk of Stroke in Male Smokers , 2000, Stroke.

[11]  Elizabeth J Johnson,et al.  Carotenoid actions and their relation to health and disease. , 2005, Molecular aspects of medicine.

[12]  A. Hofman,et al.  Dietary antioxidants and long-term risk of dementia. , 2010, Archives of neurology.

[13]  W. Markesbery,et al.  Damage to lipids, proteins, DNA, and RNA in mild cognitive impairment. , 2007, Archives of neurology.

[14]  D. Jacobs,et al.  Relationships of circulating carotenoid concentrations with several markers of inflammation, oxidative stress, and endothelial dysfunction: the Coronary Artery Risk Development in Young Adults (CARDIA)/Young Adult Longitudinal Trends in Antioxidants (YALTA) study. , 2007, Clinical chemistry.

[15]  W. Stahl,et al.  Lycopene oxidation product enhances gap junctional communication. , 2003, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[16]  David E. Booth,et al.  Analysis of Incomplete Multivariate Data , 2000, Technometrics.

[17]  W. Freeman.  Alzheimer: The Life of a Physician and the Career of a Disease , 2004 .

[18]  P. Mecocci,et al.  Plasma Antioxidant Status, Immunoglobulin G Oxidation and Lipid Peroxidation in Demented Patients: Relevance to Alzheimer Disease and Vascular Dementia , 2004, Dementia and Geriatric Cognitive Disorders.

[19]  J. Buring,et al.  Circulating carotenoids and risk of breast cancer: pooled analysis of eight prospective studies. , 2012, Journal of the National Cancer Institute.

[20]  M. Catani,et al.  Lymphocyte oxidative DNA damage and plasma antioxidants in Alzheimer disease. , 2002, Archives of neurology.

[21]  P. Bowen,et al.  Tomato Sauce Supplementation and Prostate Cancer: Lycopene Accumulation and Modulation of Biomarkers of Carcinogenesis , 2002, Experimental biology and medicine.

[22]  P. Mecocci,et al.  Plasma susceptibility to free radical-induced antioxidant consumption and lipid peroxidation is increased in very old subjects with Alzheimer disease. , 2002, Journal of Alzheimer's disease : JAD.

[23]  Tiina H Rissanen,et al.  Carotenoids and cardiovascular health. , 2006, The American journal of clinical nutrition.

[24]  S. Astley,et al.  Increased Cellular Carotenoid Levels Reduce the Persistence of DNA Single-Strand Breaks After Oxidative Challenge , 2002, Nutrition and cancer.

[25]  R. Bone,et al.  Biologic mechanisms of the protective role of lutein and zeaxanthin in the eye. , 2003, Annual review of nutrition.

[26]  L. Skibsted,et al.  The interaction of dietary carotenoids with radical species. , 2001, Archives of biochemistry and biophysics.

[27]  W. Stahl,et al.  Antioxidant activity of carotenoids. , 2003, Molecular aspects of medicine.

[28]  David Heber,et al.  Overview of Mechanisms of Action of Lycopene , 2002, Experimental biology and medicine.

[29]  L. Ferrucci,et al.  Low-serum carotenoid concentrations and carotenoid interactions predict mortality in US adults: the Third National Health and Nutrition Examination Survey. , 2011, Nutrition research.

[30]  A. Collins,et al.  Recovery of human lymphocytes from oxidative DNA damage; the apparent enhancement of DNA repair by carotenoids is probably simply an antioxidant effect , 2000, European journal of nutrition.

[31]  A. Rao,et al.  Carotenoids and human health. , 2007, Pharmacological research.

[32]  P. Mecocci,et al.  Plasma antioxidants are similarly depleted in mild cognitive impairment and in Alzheimer’s disease , 2003, Neurobiology of Aging.

[33]  E. Schouten,et al.  Serum carotenoids, alpha-tocopherol and mortality risk in a prospective study among Dutch elderly. , 2001, International journal of epidemiology.

[34]  Manabu T. Nakamura,et al.  Dietary lycopene downregulates carotenoid 15,15'-monooxygenase and PPAR-gamma in selected rat tissues. , 2006, The Journal of nutrition.

[35]  Patrizia Mecocci,et al.  High fruit and vegetable intake is positively correlated with antioxidant status and cognitive performance in healthy subjects. , 2009, Journal of Alzheimer's disease : JAD.

[36]  K. Yeum,et al.  Carotenoid bioavailability and bioconversion. , 2003, Annual review of nutrition.

[37]  Manabu T. Nakamura,et al.  Dietary Lycopene Downregulates Carotenoid 15,15′-Monooxygenase and PPAR-γ in Selected Rat Tissues , 2006 .

[38]  N. D’Orazio,et al.  Carotenoids and vitamins C and E in the prevention of cardiovascular disease. , 2012, International journal for vitamin and nutrition research. Internationale Zeitschrift fur Vitamin- und Ernahrungsforschung. Journal international de vitaminologie et de nutrition.

[39]  W. Markesbery.  The role of oxidative stress in Alzheimer disease. , 1999, Archives of neurology.

[40]  A. Hofman,et al.  Dietary Intake of Antioxidants and Risk of Alzheimer Disease , 2002 .

[41]  H. Thompson,et al.  Plasma xanthophyll carotenoids correlate inversely with indices of oxidative DNA damage and lipid peroxidation. , 2000, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[42]  R. Kuczmarski,et al.  Weight, stature, and body mass index data for Mexican Americans from the third national health and nutrition examination survey (NHANES III, 1988–1994) , 1999, American journal of human biology : the official journal of the Human Biology Council.

[43]  D. Bennett,et al.  Dietary Intake of Antioxidant Nutrients and the Risk of Incident Alzheimer Disease in a Biracial Community Study , 2022 .

[44]  Michael A. Grusak,et al.  IMPROVING THE NUTRIENT COMPOSITION OF PLANTS TO ENHANCE HUMAN NUTRITION AND HEALTH1. , 1999, Annual review of plant physiology and plant molecular biology.